M. Grieff et al., RENAL CALCITRIOL SYNTHESIS AND SERUM PHOSPHORUS IN RESPONSE TO DIETARY PHOSPHORUS RESTRICTION AND ANABOLIC AGENTS, American journal of kidney diseases, 28(4), 1996, pp. 589-595
Calcitriol [1,25-(OH)(2)D-3] synthesis by the renal 25-hydroxyvitamin
D-3-1 alpha-hydroxylase (1 alpha-hydroxylase) is induced in rats on a
low phosphorus diet, but not in the hypophysectomized (HPX) or diabeti
c rat. However, the normal response is restored by the administration
of growth hormone (GH) or insulin-like growth factor-I (IGF-I), or ins
ulin, respectively. To further characterize this in vivo phenomenon, t
he acute effects of GH, IGF-I, and insulin were studied in the HPX rat
. In the HPX rat the low phosphorus diet alone did not significantly a
lter serum phosphorus or 1 alpha-hydroxylase activity, but treatment w
ith GH resulted in a marked decrease in serum phosphorus that was asso
ciated with a fivefold induction of enzyme activity. Time course studi
es showed that by 6 hours after GH administration, hepatic IGF-I mRNA
had increased 10-fold while renal IGF-I mRNA had increased by only 52%
. Between 6 and 12 hours, serum phosphorus decreased dramatically and
1 alpha-hydroxylase activity increased twofold. Treatment of phosphoru
s-restricted HPX rats with IGF-I resulted in a decrease in serum phosp
horus by 2 hours that preceded a fourfold increase in enzyme activity
between 6 and 10 hours. Treatment of phosphorus-restricted HPX rats wi
th insulin produced similar results. This is the first demonstration o
f hypophosphatemia preceding induction of the 1 alpha-hydroxylase afte
r administration of IGF-I or insulin to the HPX rat on a low phosphoru
s diet. Although these growth factors may have a direct effect on the
1 alpha-hydroxylase, these data suggest that the influence of GH, IGF-
I, and insulin on transcellular phosphorus flux may have an independen
t effect on enzyme activity. Furthermore, the much greater induction o
f hepatic compared with renal IGF-I mRNA in response to GH suggests th
at systemic, rather than the local, IGF-I may be required for inductio
n of the 1 alpha-hydroxylase. This effect may be mediated by either th
e insulin or the IGF-I receptor. (C) 1996 by the National Kidney Found
ation, Inc.